The MSK Policy document to ensure the highest quality ... · all of MSK’s facilities, increasing awareness and availability of trials to physicians and patients, enhancing our capacity

Date Original Document created: July 2001, NCI Approved: September 2001 Date Revised: February 2007, NCI Approved: March 2007 Date Revised: March 2011, NCI Approved: September 2011 Date Revised: October 2015, NCI Approved: April 2016 Date Revised: May 2018, NCI Approved: August 2018

1 Memorial Sloan Kettering: Data and Safety Monitoring Plan

Data and Safety Monitoring (DSM) Plans

The MSK Policy document to ensure the highest quality clinical research and safety of

participants in our Clinical Research and Population Science Research Programs.



Table of Contents: Page

1. Introduction 3

2. Institutional Oversight 4

3. Protocol Review and Activation 10

4. Protocol Risk Determination 13

5. Procedures for Monitoring Clinical Trials at MSK 14

6. Quality Assurance Program 17

7. Multi-Site Compliance Coordination 22

8. Incident Reporting 22

9. Notification Requirements for Clinical Trials Sponsors 25

10. Research Misconduct 25

11. Conflict of Interest Management 27

12. Appendix 28

A. Protocol Review and Approval Flow Diagrams 29 B. Research Council Membership (Council A and B) 32 C. IRB/Privacy Board SOP List 34 D. DSM Committee Membership 36 E. DSMB Membership 38 F. OHRP Incident Report Form 39 G. Conflict of Interest Advisory Committee Membership 40



DATA AND SAFETY MONITORING (DSM) OF CLINICAL RESEARCH Introduction The following document outlines the policies established by Memorial Sloan Kettering (MSK) for the appropriate oversight and monitoring of the conduct of clinical trials supported by NIH, NCI/NCTN, Industry or MSK investigator-initiated research. MSK’s DSM Plan was originally developed to comply with the NIH/NCI policy guidance entitled “NCI’s Essential Elements of Data and Safety Monitoring Plan for Clinical Trials funded by the NCI.” The institutional DSM Plans were first approved by the NCI in September 2001, and have been modified over time to ensure consistency with the national standards, new guidances and revisions to the institutional policies and procedures. Throughout the document there are hyperlinks to MSK’s Clinical Research Portal providing easy access to relevant documents, forms, processes and Standard Operating Procedures (SOP). These policies ensure the safety of human participants in our clinical and population science research (referred to as patient-oriented research) programs, the validity and integrity of the data, and the appropriate termination or suspension of trials. The policies and procedures for DSM at MSK maintain the same operational definition of a clinical trial as noted in the NCI policies with the additions noted below. The definition of a clinical trial is: A prospective study involving human subjects designed to answer specific questions

about the effects or impact of a particular biomedical or behavioral intervention; these may include (but are not limited to) drugs, treatments, devices, or behavioral and nutritional strategies. Participants in these trials may be people with cancer or without a diagnosis of cancer but at risk for it.

In the area of molecular or imaging diagnostics, a study is considered to be a clinical trial if it uses the information from the diagnostic test in a manner that somehow affects medical-decision making for the subjects. In this way the information from the diagnostic test may have an impact on some aspect of outcome, and assessment of this impact may be a key goal of the trial.

Behavioral clinical trials include interventions whose goals are to increase behavior (e.g., cancer screening, physical activity, fruits and vegetable intake, etc.) eliminate or reduce behaviors (e.g., smoking, sun exposure) and/or improve coping and quality of life (e.g., among cancer survivors) and reduce the negative sequelae of treatment. Interventions may pertain to prevention, early detection, treatment, and survivorship. Observational studies are not considered clinical trials for this document.



In addition to the areas defined above, human subjects participating in any study where(1) a dye is injected or (2) a blood specimen is drawn or a biopsy performed (notstudies for specimen banking only) will qualify for review via the DSM mechanism asclinical trials.

The policies and procedures for DSM of the patient-oriented research programs at MSK are established and monitored by Clinical Research Administration (CRA). The CRA is a function of Memorial Hospital and the Memorial Sloan Kettering Cancer Center, and reports directly to the Deputy Physician-in-Chief, Clinical Research [Paul Sabbatini, MD] and the Senior Vice President, Research Technology Management [Eric Cottington, PhD]. A description of the protocol monitoring process, including before protocol approval to activation, and throughout the protocol life cycle is defined.

INSTITUTIONAL OVERSIGHT

The Clinical Research (CR) and Population Science Research (PSR) Programs, which make up MSK’s patient-oriented research programs, grew significantly since the last competitive renewal. This growth was based on current scientific and research related advances in cancer care. This is demonstrated by the overall increase to our clinical research protocol portfolio, therapeutic participant accruals and research staffing numbers. Figures 1 and 2 illustrate the change between 2010 and 2016 in the number of accruals to therapeutic clinical trials. Figure 1 Figure 2

0

100

200

300

400

500

600

2010 2011 2012 2013 2014 2015 2016

Non-Therapeutic Correlative/Specimen Therapeutic

541

331

219

0

200

400

600

800

1000

1200

1400

1600

1800

2010 2011 2012 2013 2014 2015 2016

Ph I, Ph I/II Ph II Ph III Ph IV Other Pilot

1609

1497

1359

4

244



The result of this rapid growth in the clinical research portfolio and accruals required an increase and demand for additional research staff to support the patient-oriented research enterprise as reflected in Table 1. Table 1:

In response to this need for additional support, we systematically evaluated in early 2016 the various components of the patient-oriented research programs. This included the pre-existing Office of Clinical Research (OCR) and the clinical departments. The evaluation included identification of stakeholders [patients, researchers and sponsors] with the goal of equalizing the opportunities for trial participation at all stages and across all of MSK’s facilities, increasing awareness and availability of trials to physicians and patients, enhancing our capacity to conduct transformative research, and improving the overall quality management of the clinical trials portfolio. This review required a comprehensive evaluation of all areas involved in CR and PSR trial support. This analysis showed areas of redundancy, inefficiency in standards and workflows, need for technology enhancements in daily operational tasks, and opportunities to centralize more key services across the patient-oriented research programs. The overall intent was to rebuild a lean infrastructure to support the growing needs of the patient-oriented research programs. The reorganization created a new entity referred to as Clinical Research Administration (CRA) which takes advantage of economies of scale while ensuring effective support for clinical research. CRA collaborates with department administration and center divisions in the development and delivery of services that are responsive to the needs of the principal investigators (PIs) and respective programs. The overall mission of CRA is to oversee the research involving human subjects at MSK ensuring that the efficient and effective conduct of the research is in full compliance with requisite federal regulations, institutional policies and the CCSG requirements for Clinical Protocol and Data Management (CPDM). The CRA is an institutional office that reports to the Deputy Physician-in-Chief, Clinical Research, Dr. Paul Sabbatini and works in conjunction with Institutional Leaders, the Protocol Review and Monitoring System (Research Council), the IRB/Privacy Board, and the Clinical and Laboratory Departments that make up the

2010 Research Position # of Staff

2016 Research Position # of Staff

Research Assistants 250 Research Assistants 478 Research Coordinators 68 Research Coordinators 196 Research Managers 26 Research Managers 43 Program Managers 8 Program Managers 11



patient-oriented research programs. Dr. Sabbatini reports to José Baselga MD, PhD, who in addition to being Physician-in-Chief of Memorial Hospital, is the Deputy Director, Memorial Hospital of the Cancer Center. The placement of the CRA within the institutional organizational structure can be found in Figure 3.

Figure 3:

CRA is an institutional level entity comprised of two primary divisions, Clinical Research Operations (CRO) and Clinical Research Compliance (CRC), each with distinct functions and responsibilities. The Clinical Trials Nursing Department has a matrix report into the CRA to provide increased integration of Clinical Trial Nurses (CTN) with the patient-oriented research teams.

The divisions (CRO and CRC) within CRA are divided into 10 units with specific core responsibilities, functions, and oversight. The units in CRO are: Protocol Operations, Clinical Research Informatics and Technology, Clinical Research Education and Outreach, and Administrative Operations. Two units within Research and Technology Management have matrix reporting into CRO, Clinical Research Finance and Clinical Research Contracting. The units in CRC are: Protocol Activation and Human Research Protection Program, Regulatory Oversight and Product Development, Multi-Site Compliance, and Quality Assurance. The organizational structure of CRA and the core responsibilities of each unit are referenced in Figure 4, described below and available on the Clinical Research Portal: Clinical Research Administration

https://one.mskcc.org/sites/pub/rtm/Pages/Clinical%20Research%20Administration/home.aspx



Figure 4

Clinical Research Operations

Protocol Operations: Stephanie Terzulli, Ph.D., Director The core responsibility of this unit is to manage the conduct of clinical research by providing services including: clinical research practice standards, oversight of clinical research data collection/data management, analysis and reporting, regulatory coordination, and guidance to investigators in planning and conducting clinical research protocols. Protocol Operations works collaboratively with MSK’s ambulatory care program and provides organizational and research management services to all of our facilities where investigational activities are conducted. Protocol Operations works cohesively with Clinical Trials Nursing and the Clinical Departments involved in the patient-oriented research programs. Protocol Operations is also responsible for the management and oversight of Protocol Core Services (PCS), a centralized core service that provides institutional resources to support the institutional biospecimen collection, management and processing of samples.

Clinical Research Informatics and Technology (CRIT): Joseph Lengfellner, Senior Manager The reorganization of the clinical research infrastructure has resulted in an expanded CRIT unit with the core responsibility of deploying technology to improve clinical research practice across the patient-oriented research programs. CRIT develops and implements new technology initiatives to enhance efficiencies in workflows for the clinical research community. This unit is also responsible for all institutional initiatives relating to clinical



research informatics. CRIT manages the centralized databases utilized by the CR and PSR Programs including but not limited to PIMS (Protocol Information Management System) which is the institutional protocol repository and used by PRMS and CPDM, the CRDB (Clinical Research Database), Medidata Rave, REDCap, and OnCore’s CTMS (Clinical Trials Management System) for active research protocol management and reporting. Clinical Research Education and Outreach: Mayra Nicola, Manager This unit’s core responsibility is to provide interactive education with post-education assessments for all levels of staff involved in clinical research to ensure safe, efficient, and informative clinical research via awareness and knowledge of relevant procedures, processes, and regulations. This group also tracks certification dates on required Human Subjects Protection and Good Clinical Practice training. All new clinical research staff are required to attend an intensive multi-day orientation which includes an overview of clinical research methodology and an introduction to various research-related processes at MSK. The Education and Outreach unit is in the process of revising and/or developing new trainings focused on particular research concepts and processes which will be open to all staff across CR and PSR including, an introduction to the RSA role, consenting principles (basic to complex), and Serious Adverse Event (SAE) reporting. Administrative Operations: Lawrence Lupkin, Senior Manager This unit’s core responsibilities include the financial management and revenue tracking of CRA services, managing the day-to-day administrative and operational management of CRA, working across MSK as needed in areas like Human Resources, Facility Management, Business and Disaster Recovery, and other such administrative duties that are essential in a large division like CRA. Clinical Research Finance: Barry Zakrzewski, Director The core responsibility of this unit is to provide centralized oversight for the fiscal management of clinical research studies, ensuring an efficient, compliant, and transparent process. A dedicated team within this unit has been established to develop budgets in collaboration with appropriate study team members, and to ensure protocol recovery. This until will reconcile variances between the protocol budget and expense. Clinical Research Contracting: Lee Stetson, Assistant General Counsel The core responsibility of the CR Contracting unit is to provide contracting and legal services focused on the timely negotiation and execution of clinical trial agreements (and associated amendments) in support of the CR and PSR Programs. The Clinical Research Contracting unit has embarked on several key initiatives: 1) developing master clinical trial



agreements where possible with pre-negotiated language to accelerate time to protocol activation, 2) adopting uniform standard operating procedures with the goal of streamlining negotiations. Clinical Research Compliance Protocol Activation/Human Research Protection Program (HRPP): Ann Rodavitch, Director The Protocol Activation and HRPP unit has the dual responsibilities of providing guidance, standardized processes and assistance with regards to protocol development including review and approval and provides leadership oversight of the HRPP. There are three sub-groups within this unit, each focused on a specific aspect of trial activation: Protocol Activation Core, Protocol Review Core and the HRPP Office. Regulatory Oversight and Product Development: Richard Ellis, Manager The Regulatory Oversight and Product Development unit has the core responsibility for ensuring Investigators and research staff across the patient-oriented research programs adhere to institutional standards and federal regulatory requirements of the FDA, NIH, and OHRP with respect to investigational drugs, devices and biologics for all MSK-sponsored IND trials and MSK-manufactured products. This unit also oversees the management of MSK’s Investigational New Drug and Device (IND/IDE) Program, providing guidance to MSK Investigators on product development strategy and preclinical requirements for MSK’s IND/IDEs including preparation of IND applications and technical documents for regulatory agencies. Multi-Site Compliance: Mary Warren, Director The Multisite Compliance unit is responsible for regulatory and quality oversight of MSK’s patient-oriented research being conducted at sites and centers in addition to MSK. MSK has expanded our CR and PSR opportunities in the community through the MSK Alliance Program, operation of our multisite clinical trials portfolio including the POETIC (Pediatric Oncology Experimental Therapeutics Investigators Consortium), and oversight of the NCI-supported portfolio including the NCTN U10 Grant and the NCI-supported clinical trials portfolio. The unit is increasingly taking on direct oversight of protocol activation, regulatory compliance and quality performance of the above to allow research staff to focus on protocol oversight and data management. Clinical Research Quality Assurance (CR QA): Karima Yataghene, M.D., Director The core responsibility of QA is to provide leadership in quality and regulatory oversight to minimize risk and to ensure reliable, quality management services to support the overall



success of CR and PSR programs. The QA unit ensures that the Institution is in compliance with Good Clinical Practice and Good Manufacturing Practice guidelines and adheres to all federal regulatory requirements. Since the last Competitive Renewal this unit has been reorganized into three teams organized by functional responsibility: Audits, Monitoring Visits, and Investigational Product QA. The QA programs were reevaluated and new QA processes for protocol selection, databases/systems, eligibility verification and investigational drug pharmacy were implemented. QA is also responsible for the oversight and management of MSK’s Data and Safety Monitoring (DSM) plans in collaboration with the Protocol Activation and HRPP unit. The CRA has a total of 219 staff on its table of organization. The division reports to Paul Sabbatini, MD, Deputy Physician-in-Chief, Clinical Research and the Senior Vice President, Research Technology Management, and is led by Dorothy Damron (CRO) and Collette Houston (CRC). The CRA has a senior management team led by Ms. Damron and Ms. Houston. The qualifications, experience and responsibilities of the leadership team are described below. Dorothy Damron, VP, Clinical Research Operations, has been involved in research for 35 years. Prior to coming to MSK, she spent 13 years as Director of the Clinical Research Office at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins. Ms. Damron has been involved in clinical research operations at MSK since 2015. Collette Houston, VP, Clinical Research Compliance, has been involved in clinical research activities and management at MSK for the last 30 years. Ms. Houston oversees the overall compliance of the patient-oriented research programs. PROTOCOL REVIEW AND ACTIVATION In order to improve efficiency, maximize experience, and enhance the throughput we have centralized the staffing resources involved in protocol review and activation. This includes a team of experts who shepherd the protocol through the review process including quality review, writing consent forms, responding to review committees and facilitating the communications between the PI, Study Team and the Review Committees. This effort has significantly aided in improving the overall time to protocol activation. To compliment this effort, we have also centralized the administrative management team that supports all of the protocol review committees. The protocol activation workflows can be found in Appendix A and on the CR Portal: Protocol Review Flows. The protocol sponsor will determine the appropriate committee reviews that are required, with MSK investigator

https://one.mskcc.org/sites/pub/clinresearch/Pages/protocol-review-committees/protocol-review-flows.aspx



initiated research protocols requiring the most steps in the review process including but not limited to: Primary/Participating Department Review, Research Council (Scientific Peer Review) and IRB/Privacy Board. Depending on the protocol intervention and the regulatory requirements of the protocol, additional review committees may be required (e.g., Committee on Radiation, Investigational New Drug/Device Committee, etc). The primary steps in the MSK Investigator-Initiated studies are described below and demonstrated in Figure 5. Primary Department/Participating Department: The primary department will review the protocol for scientific merit, quality, programmatic fit within the disease/service portfolio, and resource allocation. If the Co-Principal Investigator is from a different clinical department, that department must evaluate the impact of the protocol on the department (e.g., patient referrals, involvement in the intervention, etc) and either provides a full review similar to the primary department, or an expedited review and sign-off which equates to a commitment to participate in the study. Committee on Radiation (COR): This committee is a committee mandated by the federal, state and city regulations and is charged with developing policy for and monitoring the use of radioactive materials and exposure in the Center. COR is required to review all protocols investigating the use of radioactive materials in humans including radiolabeled antibodies. COR evaluates the safety of the protocols related to the radioactive materials and radiation exposure. Regulatory Committees: Protocols that involve the use of non-FDA approved drugs, devices and/or radionuclides are required to be reviewed by either the Investigational New Drug/Device Committee or the Radioactive Drug Research Committee prior to the IRB/Privacy Board review. The Investigational New Drug/Device Committee is required for any MSK

investigator initiated protocol that is utilizing a non-FDA approved drug or device or one being used for an unapproved indication in a manner that would require the filing of an IND/IDE.

The Radioactive Drug Research Committee is mandated by the FDA and is required for any study that uses radionuclides to probe biological processes including physiology, pharmacology or biochemistry in humans. These protocols almost always involve the administration of tracer doses and are not focused on therapeutic endpoints or demonstrating safety or efficacy.



Research Council: Oversees the protocol review and approval process at MSK and is the scientific review committee mandated by the NCI. It is a multidisciplinary institutional committee whose charge is to review proposed research protocols for quality, scientific merit, institutional priority, programmatic fit, and resource allocation while promoting timely protocol activation. The Research Council Membership can be found in Appendix B and on the CR Portal: Research Council.

The Research Council also reviews studies that are not meeting the Center’s Core Grant (CCSG) expectations on accrual performance. The expected time to complete a clinical study is less than 5 years. The clinical study portfolio is reviewed twice a year. A Principal Investigator who has a clinical study that is not meeting accrual expectations will be asked to provide an action plan to improve study performance. The Research Council will review the plan and determine if it is sound and should be pursued or if the study should be closed with the IRB/PB.

All protocols reviewed and monitored by MSK Research Council and that are open for accrual will be reviewed for scientific progress every six (6) months. Protocols identified as non-performing must be addressed as outlined the Research Council Non-Performing Protocol Review NP Protocol SOP.

IRB/Privacy Board: Oversees the protection, rights and welfare of the human subjects who participate in our clinical research portfolio, evaluating the overall risk versus benefit ratio to the participant. The IRB/Privacy Board reviews all protocols, informed consent documents, grants involving human subjects, protocol amendments, annual reviews, safety profiles, adverse events, and unanticipated problems. A list of Standard Operating Procedures that govern the IRB/Privacy Board can be found in Appendix C and on the CR Portal: IRB/Privacy Board SOPs.

Figure 5

+ If applicable

https://one.mskcc.org/sites/pub/clinresearch/Pages/protocol-review-committees/research-council.aspx

https://one.mskcc.org/sites/pub/clinresearch/Policies/CR%20420.pdf

https://one.mskcc.org/sites/pub/clinresearch/Pages/policies-and-regulations/irb-pb-standard-operating-procedures.aspx



NCI and/or NCTN Protocol Activation

All NCI approved protocols go through an extensive protocol development and review process through the NCI’s different mechanisms (i.e., Cooperative Group, Clinical Trials Evaluation Program, Experimental Clinical Trials Network, etc.) which include NCI approval and submission to the NCI’s Central IRB. The protocol then passes through the MSK IRB/Privacy Board for local privacy review and approval.

PROTOCOL RISK DETERMINATION Risk determination is a critical part of the evaluation process. The protocol risk category is defined by the Principal Investigator and reviewed and approved by the IRB/PB. This determination is made by utilizing the following criteria: Risk Category Definitions

Low Probability of harm/discomfort not greater than daily life or routine physical/psychological exams 45 CFR 46.102(i) Examples: Survey research, venipuncture, taste and observation studies, non-contrast MRI studies, non-invasive procedure

Moderate Intervention commensurate with those inherent in their expected medical, social, or education situations. Risks are reasonable in relation to anticipated benefits and the importance of knowledge expected to result 45 CFR 46.111(a)(2) 21 CRF 50.3k Examples: Investigations drug/device, therapeutic research including but not limited to surgery, radiation therapy, chemotherapy, vaccines, biologics.

High Greater than minimal risk which may or may not have direct benefit to the subject. Risks are high in relation to anticipated benefits. Examples: Gene transfer, First in human Phase 1, Studies of new articles having high/severe pre-clinical toxicity but may be commensurate to the potential benefit.

There are additional risk categories for clinical trials involving children and investigational devices. Please refer to the following links on the Clinical Research Portal for more information: Children Risk Level and IDE Risk Level. The protocol specific risk determination is taking into consideration when assigning the Data and Safety Monitoring (DSM) review cycle.

https://one.mskcc.org/sites/pub/clinresearch/Pages/developing-a-new-study/Risk%20Category%20Definitions.aspx

https://one.mskcc.org/sites/pub/clinresearch/Pages/developing-a-new-study/Risk%20Category%20Definitions.aspx#TabH1Group7

https://one.mskcc.org/sites/pub/clinresearch/Pages/developing-a-new-study/Risk%20Category%20Definitions.aspx#TabH2Group7



PROCEDURES FOR MONITORING CLINICAL TRIALS AT MSK

There are several different mechanisms by which clinical research studies are monitored for accrual performance, data, safety and quality at MSK. The Principal Investigator (PI) is ultimately responsible for the conduct and monitoring all aspects of a trial on an on-going basis. In addition to the PI, there are institutional processes in place for quality oversight through the Research Council, Data and Safety Monitoring Committee and Board, and the Quality Assurance Unit in CRA. Data and Safety Monitoring Committees MSK has established two distinct monitoring oversight committees that have responsibility to provide data and safety monitoring over our clinical trials program focused primarily on MSK sponsored, investigator-initiated research, but as necessary will review protocols from other sponsor types (Industrial, External Peer Reviewed, NCI/NCTN), as needed. The two committees, Data and Safety Monitoring Committee (DSMC) and Data and Safety Monitoring Board (DSMB) report up to the Deputy Physician-in-Chief, Clinical Research. Data and Safety Monitoring Committee (DSMC), Chair: Eileen O’Reilly, MD The DSMC provides oversight for nearly 600 active clinical trials at any given time. The committee monitors the risk participants are exposed to, the progress of the study, the adequacy of data collection and management, and confirms that the trial is proceeding as expected. The DSMC is responsible for monitoring all Phase I, I/II, II, Pilot, and non-phase based clinical trials, including but not limited to therapeutic, investigational device, nutritional, diagnostic, prevention, behavioral, quality of life and some correlative science trials, when deemed appropriate. At the time of study activation it is determined whether the trial will be monitored by DSMC, and at what frequency (quarterly, bi-annually or once a year). This determination takes into consideration the following: Adherence to the NCI definition of a clinical trial (defined on page 3) Protocol sponsor/funding source Protocol Risk Accrual rate and estimated time to accrue External oversight or monitoring provided through another source



The DSMC consists of twenty-two members from throughout the Center with various areas of expertise including a Biostatistician. There is one external member who is critical to evaluating DSM for studies with Institutional Conflicts. The external member is important to the review process, ensuring and protecting against any potential conflicts. The list of DSMC membership can be found in Appendix D.

The DSMC members receive all relevant materials for each of their assigned trials prior to the committee meeting. Review assignments are determined by the member’s clinical expertise, study modality, and patient population. Review assignments are vetted to ensure there are no conflicts of interest between reviewers and their assignments. If DSMC members have conflicts during the meeting, they are asked to recuse themselves from the discussion and vote.

Each study is reviewed with the following questions in mind: 1. Are patients being exposed to unanticipated or excessive toxicity? 2. Is enrollment proceeding according to projections; has accrual target been met? 3. Are the protocol specific rules being followed as per protocol (e.g., dose escalation in

a Phase I, response assessment, etc.)? 4. Are early stopping rules being enforced? 5. Are sufficient data being collected/entered to effectively assess study progress?

Each study is evaluated prior to the meeting by the assigned reviewer. Protocols with any issues and/or concerns are discussed. Approval actions are determined, and communicated to the PI and the Research Team in an official memorandum. Committee meeting actions/outcomes are stored in electronically in PIMS (Protocol Information Management System) along with all other review committee and monitoring activities in the Protocol Activation and HRPP Unit. Should a study not be approved, the PI has 14 days to provide a written response to the DSMC’s concerns; if the response is not satisfactory to the reviewer, it will return to the committee for discussion and possible escalation to the Deputy Physician-in-Chief, Clinical Research (Institutional Official).

Data and Safety Monitoring Board (DSMB), Chair: Colin Begg, Ph.D. The DSMB provides monitoring oversight to MSK investigator-initiated (IIT) Phase III randomized clinical trials, or any Phase III trial that is not reviewed by an independent review board. The DSMB conducts a comprehensive review of the trials focusing on study endpoints and outcome data, as well as study accrual, toxicities, unexpected adverse events, risks to participants, the overall progress of the study, and the adequacy of data collection and management. This review process provides the PI with guidance and



recommendations throughout the life of the study, ensuring the PIs ability to carry out the study as designed. The DSMB meets annually (typically in June) and is comprised of six voting members, four of whom are unaffiliated with MSK. The DSMB Chair is one of the two MSK voting members. The DSMB Membership list can be found in Appendix E. The majority of the DSMB members are external, and therefore eliminates the potential for study reviewer conflicts and/or bias. The area of expertise represented across the DSMB reflects the diversity of proficiency necessary to review the various aspects of the MSK IIT Phase III portfolio. If a given study has Investigator and/or Institutional Conflict, the reviewers are aware of the conflict, and their responsibility to consider the conflict when evaluating the study quality and outcomes. The DSMB Chair asks members to recuse themselves from a discussion and voting based on their own personal conflicts.

Prior to the annual DSMB Meeting, individual PIs must submit a summary report including the following information:

Accrual information, including planned accrual goals and timelines Participant eligibility and compliance Comprehensive summary of side effects/toxicities experienced Comprehensive statistical analysis of the study endpoints including blinded

outcome data Any actions the PI has taken based on prior DSMB review and recommendations

The DSMB Members receive a complete packet of all protocols to be discussed several weeks prior to the meeting; if a protocol was reviewed in prior years the previous year’s recommendations are also included in the packet. Board members review these packets prior to the annual meeting and come with questions and concerns for discussion. At the meeting the PI and study statistician are present, and given an opportunity to discuss the progress of the study and to answer any additional questions the board members may have. Following the dialogue, the PI will leave and the board members have time to further discuss the study and vote. In the case of blinded trials, the interim analysis is submitted separately by the protocol Biostatistician, and is discussed at the meeting only with the statistician present.

Each PI will receive official notification from the DSMB with their overall feedback on the study progress, any recommendations they have to improve the study, and the final voting outcome. The PI’s sponsoring department and study statistician will be copied on the PI correspondence. Minutes of the DSMB’s proceedings are produced summarizing the



discussions for each study, and the board’s recommendations. The comprehensive minutes and outcomes are shared with the Deputy Physician-in-Chief for Clinical Research and the Board Members. The IRB Chair and the Human Research Protection Program Office receives all recommendations made by the board. The meeting minutes are maintained in the Protocol Activation and HRPP Unit.

CLINICAL RESEARCH QUALITY ASSURANCE PROGRAM: CR QA Audit Program Another mechanism in place for the data and safety monitoring of human subjects participating in clinical trials is through the auditing program. All active MSK protocols and databases are eligible for auditing, including investigator initiated, NCI, and pharmaceutically sponsored. In addition, studies may be audited by external groups such as: pharmaceutical companies, cooperative groups, or the NCI. Audits are conducted to ensure compliance with federal regulations (21 CRF 50, 21 CRF 56, 21 CFR 312, 45 CRF 46), Good Clinical Practice (GCP) guidelines and MSKCC Clinical Research Audit Guidelines. Protocol Compliance Auditing There are two levels of protocol compliance auditing. Each level of auditing covers the same quality review of both protocol compliance verification and source data quality accuracy. The first level of auditing is institutional, and conducted by Clinical Research Quality Assurance (CR QA). The second level of review is a quality control review conducted by the research staff in the clinical department of the Principal Investigator. Institutional Audits Conducted by CR QA CR QA conducts audits on trials for consent, eligibility, protocol compliance, regulatory document completeness and verification that database data entry is accurate and complete. The following procedure is used to ensure adherence to all policies: Protocols are chosen randomly across all MSK clinical departments and/or can be

performed at the request of any institutional department, CRA leader or PI. The PI, department leaders and research staff are notified of the upcoming audit, the

study being audited and the audit start date. All audits are projected to be completed within 1-2 weeks.

Protocol specific audit forms are created focusing on adherence for all areas under

review in the audit (e.g. consent, eligibility, treatment, baseline and on-study testing evaluations, guidelines for assessment of toxicity and outcome and data entry verification).

https://one.mskcc.org/sites/pub/rtm/Pages/Quality-Assurance-Unit.aspx



Approximately four to six participants are audited on each trial and are randomly

chosen over the entire course of the study. Additional cases can be selected if deemed appropriate.

Protocol regulatory binders and participant electronic medical records, office

research files and database printouts are reviewed to evaluate compliance and data verification.

It is the responsibility of the department staff to retrieve any records on selected

participants who are registered at outside sites who have been selected for audit. The compliance part of the review consists of 100% verification of the protocol

specific requirements in the areas under review, for all selected participants. A standardized audit report which summarizes the audit findings and resulting

recommendations is compiled by CR QA and reviewed by the Manager, Clinical Research Audits and the Director, CR QA.

The PI is given an appropriate timeframe to respond to any major deficiencies noted

in the report with a corrective and preventative action plan to be implemented within his/her service/department. Acknowledgment of the receipt and adequacy of the plan is sent to the protocol PI and research staff.

CR QA can choose to re-audit any trial where major deficiencies were found. This is

done after sufficient time has allowed for accrual of new participants and is done via the routine procedure already outlined.

External Site Audit/Inspection Preparation CR QA is responsible for the oversight and coordination of research teams that prepare for MSK audits by external groups (e.g. cooperative groups, federal agencies, and industrial sponsors). CR QA leads and facilitates the audit planning, day of audit activities and post audit activities when the audit involves a federal agency or multiple clinical departments or at the request of the PI. The following procedure is used to ensure that the institution is organized and well prepared for these audits: Upon receiving notification of an upcoming audit, the appropriate personnel from

the departmental research team, CR QA, IRB/PB, Clinical Information Center, Pharmacy, Radiology, Clinical Lab Department and the Conference Planning Department are notified.



The external auditor is contacted to confirm logistics of the audit/inspection in order to plan appropriately (e.g., number of auditors, meetings to occur, etc.).

CR QA staff in collaboration with the PI(s) and Research Study Teams ensures that

all pre audit preparations are completed in a timely manner, these include but are not limited to: identify appropriate space with computer/EMR, printer and phone access, identify research staff to assist auditor, ensure availability of PI, and create any necessary key staff contact lists.

The Pharmacy Department conducts the review of participant drug doses and drug

accountability. All source documents are prepared and reviewed prior to the audit. CR QA pre audits Regulatory Binders to ensure completeness and accuracy in regard

to: protocol/consent versions, IRB/PB documents/approvals/ SAEs/safety reports, protocol violations, any correspondence between MSK and sponsor or IRB/PB or FDA, Lab certifications/NL ranges, federal forms (1571, if applicable and 1572), investigator CVs and investigator’s brochure.

A pre audit of participant cases is also conducted for protocol compliance, source documentation (EMR chart completeness), and verification of data accuracy on CRFs or electronic data submissions and compliance with data submission timetables.

The designated audit lead prepares a summary of pre audit findings to inform the PI

and CRA leadership of any noted deficiencies. During the audit, a CR QA audit team representative is available to ensure logistics

of the audit/inspection are managed appropriately. It is the responsibility of the PI and Research Team to draft the initial audit response

from MSK. If multiple PIs/departments are involved, CR QA will help facilitate the institutional response. The Manager, CR Audits and Director, CR QA will review and approve any response to an external audit/inspection before finalized and distributed.

Documentation of all institutional, departmental and external site audits (e.g., audit notification, audit reports and corrective action plans) is maintained in the Protocol Information Management System. Clinical Research Monitoring Program The Clinical Research Monitoring Program developed in 2010 is another mechanism for the data and safety monitoring of human subjects participating in clinical trials. Monitoring is an ongoing process for overseeing the progress of a research study, and of ensuring that it is conducted according to the protocol, institutional SOPs, Good Clinical Practice (GCP) and



applicable regulatory requirements. The MSK CR Monitoring Program focuses on trials where MSK is the sponsor, and places priority on MSK-held IND/IDE trials and/or Multi-Center Trials. Monitoring priority is determined by study risk, protocol status (percent complete), rate of accrual, trial complexity and serious adverse event reporting. A series of monitoring forms, tools and templates including a Monitoring Checklist, MSK Clinical Research Monitoring Guide for Major Protocol Deficiencies and Sample Summary Monitoring Letter are utilized to ensure standard and consistent monitoring practice across CR QA. These tools are available on the CR Portal under QA, linked above. Monitoring focuses on the study-specific primary objective and the data required to answer these objectives. Monitoring visits are scheduled every 4-6 weeks based on current rate of accrual. Monitoring findings are reported to the PI and study team. Recommendations are made to the study team on methods to improve protocol compliance, data accuracy and regulatory reporting. The Deputy Physician-in-Chief of Clinical Research is alerted to any ongoing unresolved issues or unacceptable visit findings. The Clinical Research Monitoring Program uses the following enhancements to improve review: Eligibility Verification Throughout the year CR QA ensures real-time participant/patient eligibility through a verification process. The CR QA Monitoring Program selects a randomized sample of clinical trial patient registrations completed in the Clinical Trial Management System (CTMS) to review the eligibility checklist for quality assurance compliance. The eligibility checklist verification review ensures both that participants are eligible when registered to the protocol and that the eligibility checklist captures the protocol’s eligibility criteria accurately and appropriately. The program prioritizes eligibility verification based on MSK clinical trial risk level, complexity and any known historical issues. Eligibility checklist verification findings are immediately communicated with the study team’s Clinical Research Manager (CRM), Program Manager (PM), Clinical Trial Nurse (CTN), and Principal Investigator (PI) for instant resolution.

Monitoring and Auditing Tracking System (MATS) MATS is an automated, online feedback system that is used, under the oversight of CR QA, to collect feedback from industrial monitors, share feedback with MSK study teams in real-time, request auditor access, and store relevant tracking data in a database.



Using this system, the CR QA Monitoring Program evaluates real-time feedback from Industrial Sponsors, monitors trends, evaluates data, and implements changes to improve the efficiency of the CR Monitoring Program and process. CR QA escalates emergent protocol compliance, data quality or process concerns to the PI and CRA Leadership. PIs are expected to rectify issues and concerns in a timely fashion, and the CR QA Team tracks their responses for completeness and Monitor oversight. Pharmacy Review Program Another mechanism in place for safety monitoring of human subjects participating in therapeutic clinical trials is through the pharmacy auditing and monitoring program. CR QA is responsible for conducting pharmacy QA review as part of the protocol audit, a monitoring visit and pharmacy investigational product (IP) operational audit similar to that of our industrial sponsors and external federal agencies. Review involves preparing QA review reports of observation/findings and evaluating the implementation of the agreed upon corrective and preventive action plan (CAPA). Types of QA Reviews: Pharmacy QA review as part of protocol audit: Pharmacy protocol audits are conducted

as required (when a protocol is selected for audit) to assess whether pharmacy is compliant with internal standards and regulatory requirements (i.e., U.S. Food and Drug Administration (FDA), Good Clinical Practice (GCP), etc).

Pharmacy QA review as part of Monitoring visit: Pharmacy monitoring visits are conducted based on accruals or at least every six months to access whether pharmacy complies with internal standards and regulatory requirements (i.e., FDA, GCP, etc).

Pharmacy IP Operational Audit: Pharmacy operation audits are conducted annually to assess whether pharmacy operations comply with internal standards and regulatory requirements (i.e., FDA, GCP, etc) and to provide an opportunity for continuous improvement.

“For Cause” Audits: Following the identification of a serious issue related to the pharmacy QA review and pharmacy IP operations, CR QA may determine additional monitoring or auditing of the pharmacy is required. The goal will be to impart renewed structure or control, and thus ensure the quality of the pharmacy operation. The findings of a “For Cause” audit will be reported within 60 days to the Management Review Committee (MRC). The remediation of audit findings will be fully documented & reported to the MRC at the next scheduled meeting. Following a “For Cause” audit, the



pharmacy will be monitored by CRQA until demonstrating the risk of reoccurrence is acceptable.

With all type of QA review, CR QA issues a report listing any findings and/or observations found during the review. All findings are communicated with the study team, pharmacy and CR QA for resolution. MULTI-SITE COMPLIANCE COORDINATION Multi-Site Compliance

Multi-Site Compliance Unit comprises of four clinical research sub-units: the Multicenter Office (MCT Office), Clinical Research Strategic Partnerships, NCI Network Program, and the POETIC Consortium.

The MCT Office is charged with the oversight and management of multicenter trials (MCTs) where MSK serves as the Data Coordinating Center and external sites accrue participants. The MCT Office establishes and monitors compliance with multicenter policies, conducts staff training, and coordinates regulatory, protocol operations activities, and data monitoring of external participating sites.

The Clinical Research Strategic Partnerships oversees and manages a team of dedicated research staff who liaise between Alliance Members, CR Strategic Partners, MSK, and the Industrial Sponsor as needed to identify appropriate studies, facilitate study activation, oversees and ensures regulatory compliance and data quality as well as payment for clinical trial activity.

The NCI Network Program provides efficient and effective regulatory and quality management of NCI sponsored trials. In the Department of Medicine, these studies have been centralized under the NCI Network Program. In 2018, we’ll be incorporating studies from all other departments to ensure consistent portfolio management by creating standardization, and providing resources to all study teams.

The POETIC Consortium is comprised of a network of leading academic medical centers. Our members serve a geographically and ethnically diverse patient population, with an emphasis on comprehensive cancer care and research.

INCIDENT REPORTING

MSK is obligated to report certain types of incidents in human subject’s research to the Office for Human Research Protection (OHRP). The following is the regulatory background o n this reporting obligation, excerpted from the May 27, 2005 Guidance on Reporting Incidents to the OHRP.

https://one.mskcc.org/sites/pub/rtm/Pages/Quality-Assurance-Unit.aspx



HHS regulations at 45 CFR 46.103(a) and (b)(5) require that institutions have written procedures to ensure that the following incidents related to research conducted under an OHRP-approved assurance are promptly reported to OHRP:

Any unanticipated problems involving risks to subjects or others;

Any serious or continuing noncompliance with this policy or the requirements or determinations of the IRB/PB; and

Any suspension or termination of IRB/PB approval.

The HRPP (Human Research Protection Program) Office handles the reporting of incidents to the OHRP. Clinical research staff can report information relating to potentially reportable incidents to the HRPP Office via SAE report, deviation report, or memo. In addition, any potentially reportable incidents identified via any of the other monitoring procedures described in the MSKCC DSM plan will utilize the same mechanism. The IRB Chairman, HRPP Director, and HRPP Office staff will review all potentially reportable incidents. If it is determined that an incident may constitute a reportable event, the event and a proposed management plan is drafted using the OHRP Incident Report Form, Appendix F . The report is reviewed at a full board IRB meeting, and the board votes on 1) whether or not the event constitutes a reportable incident and 2) to either accept the proposed management plan or to require additional actions that might be required to protect the safety, welfare, or rights of research participants. The HRPP Office handles all reporting and follow-up correspondence with the OHRP. The IRB/PB SOP for Unanticipated Problems can be found: UP SOP. Adverse Event Reporting

An adverse event can occur on any clinical trial. It is the responsibility of the Principal Investigator and his/her research team to identify, review and report all necessary adverse events to the institutional IRB/PB, the sponsor, and participating institutions, as appropriate. The SAE Manager will report to governmental agencies (i.e., FDA), if necessary. Adverse events should be identified through standard, routine protocol review and clinical assessment of each subject participating in the clinical trial. This review should be timely in order to meet the requirements for adverse event reporting defined below.

Procedures for Assuring Compliance for Adverse Event (A E) Reporting

Federal guidelines require the timely reporting of any unanticipated toxicities/events/side effects while a participant is on a research protocol. Investigators must follow the guidelines for timely reporting of adverse events as outlined in the protocol by the institution, sponsor, or cooperative group. All serious adverse events (SA Es), regardless of

https://one.mskcc.org/sites/pub/clinresearch/Policies/IRBPB%20RR%20409.pdf



the type of research study, phase or sponsor must be reported to the MSKCC IRB/PB. SAE reporting is required from the time the participant/LAR signs the informed consent through 30 days after the last date of treatment or intervention, unless otherwise specified in the protocol. Appendix R is specifically designed for an AE experienced on a NCI sponsored clinical trial supported by a grant or contract funding. The investigator/ researcher must be familiar with the specific reporting requirements of their sponsor.

Adverse Event (A E)

An adverse event is defined by the GCP as an undesirable experience occurring to a participant during a clinical trial, whether or not considered related to the investigational product(s).

Serious Adverse Event (SA E) SAE Reporting

A serious adverse event is an adverse event that results in ANY of the following outcomes:

Death

A life-threatening adverse event

An adverse event that results in inpatient hospitalization or prolongation of existing

hospitalization (Note: a hospital admission for a planned procedure/disease treatment is not considered an SAE)

A persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions

A congenital anomaly/birth defect

Important Medical Events (IME) that may not result in death, be life threatening, or require hospitalization may be considered serious when, based upon medical judgment, they may jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the outcomes listed in this definition

Unexpected Adverse Event An unexpected AE is an experience not previously reported (in nature, severity or incidence) in the current Investigator's Brochure or general investigational plan or protocol document. Outside Safety Report A report of an SAE experienced by a subject not enrolled on trial through MSK

https://one.mskcc.org/sites/pub/clinresearch/Pages/protocol-management/serious-adverse-event-reporting.aspx



Institutional Serious Adverse Event Manager

MSKCC has identified the need for an Institutional SAE Manager who will work with the IRB/PB Chairman, HRPP Office staff, and Clinical Research Administration. The SAE Manager will be responsible for providing expertise in the area of adverse events and serious adverse event reporting. The SAE Manager will facilitate the AE and SAE activities, monitoring and reporting to the IRB/PB, regulatory agencies (e.g., NCI, NIH, and FDA) and industrial sponsors. All reported SAEs related to clinical trials conducted at MSKCC are entered into CRDB.

The SAE Manager generates queries from PIMS as needed on incomplete and outstanding SAE reports that have not been submitted to the SAE office and sends them to the clinical department’s Research Manager and Research Data Coordinators for resolution.

Lastly, the SAE Manager will assist the IRB/PB Chairman and IRB/PB Office staff on the necessary education, training and practice of adverse event reporting as per the federal regulatory guidelines.

NOTIFICATION PROCEDURES FOR CLINICAL TRIALS SPONSORS

If, through any of the internal data and safety monitoring procedures or clinical trials auditing/monitoring mechanisms, a decision is made to temporarily close or suspend a trial based on the information identified, then it is the responsibility of the individual reporting body (i.e., Principal Investigator, Clinical Research Administration, DSMC, DSMB, QA Office, Clinical Department, etc.) to notify the VP, Clinical Research Operations and VP, Clinical Research Compliance, of the temporary closure or suspension. The official closure and/or suspension information should be described in detail, and a procedure for corrective action should also be identified. The PI will review the information and report it appropriately to the sponsoring federal agency or study sponsor.

Simultaneously, a similar report of information and corrective action should be forwarded to the Deputy Physician-in-Chief for Clinical Research, and the IRB/Privacy Board Chairman. The other federal regulatory agencies will be contacted, as appropriate (e.g., OHRP and FDA). RESEARCH MISCONDUCT Research Misconduct SOP MSK is committed to the responsible conduct of research, and has policies and procedures in place for responding to allegations of misconduct in science. Allegations of research misconduct will be reviewed promptly, thoroughly, and objectively, with concern for the rights, reputations, and privacy of all those involved.

https://one.mskcc.org/sites/pub/rtm/Policies/RTM-1001.pdf



MSK policies and procedures that guide the manner in which all allegations of misconduct in science are handled, regardless of the funding source. It is written to conform to federal regulations (see 42 CFR Part 93 “Public Health Service Policies on Research Misconduct” or ORI DHHS Policy), as is required for managing misconduct proceedings that involve research support from agencies of the U.S. Public Health Service (PHS), including the National Institutes of Health. If the source of funding for the work in question is not an agency of the U.S. Public Health Service, these policies and procedures will be followed, but reporting to the Office of Research Integrity (ORI), PHS, is not required. Definition of Research Misconduct Misconduct in science is defined as fabrication, falsification, or plagiarism in proposing, performing, or reviewing research, or in reporting research results. Fabrication is making up data or results and recording or reporting them. Falsification is manipulating research materials, equipment, or processes, or

changing or omitting data or results such that the research is not accurately represented in the research record.

Plagiarism is the appropriation of another person’s ideas, processes, results, or words without giving appropriate credit.

Research misconduct does not include honest error, differences in opinion, or authorship or collaboration disputes. The Principals Responsible for Managing Misconduct Proceedings Research at MSK is conducted under the auspices of either the Sloan Kettering Institute (SKI) or Memorial Hospital (MH), or both, and is overseen by Program Chairs (in SKI) or Department Chairs (in Memorial Hospital) and by subordinate laboratory heads and service chiefs. When allegations of misconduct arise, a number of individuals with oversight of research may become involved, but the person with primary responsibility is the Senior Vice President, Research and Technology Management, who is the Research Integrity Officer (RIO). The RIO is responsible for assessing allegations of research misconduct, overseeing inquiries and investigations and other matters described in this policy.

http://www.ori.dhhs.gov/documents/42_cfr_parts_50_and_93_2005.pdf



CONFLICT OF INTEREST MANAGEMENT COI SOP

The Conflict of Interest Advisory Committee (COIAC) is a standing body appointed by the President of the Center; it is responsible to review and adjudicate situations in which a Covered Person is engaged in an Outside Activity that may be in conflict with any of his or her job duties, as set forth in the Policy on Conflict of Interest and Conflict of Commitment. Collaborations between academic health professionals and the private sector provide many societal, institutional and individual benefits. At the same time, these relationships can give rise to conflicts of interest or conflicts of commitment. Such conflicts may compromise - or appear to compromise - the integrity and objective of research, education and patient care, which in turn undermines public trust in our work. MSKCC’s policy is designed to assist the investigator and the Center in identifying and managing situations that can give rise to conflicts. The COIAC membership can be found in Appendix G.

Any investigator, who is determined to have an individual Conflict defined by the COIAC, requires a Management Plan describing the permitted activities for that individual related to the human subjects’ research. Each Management Plan is specific to the research the individual is involved in, taking into consideration the study design, risk level, study management in relation to the conflict. All Management Plans are reviewed and approved by the MSK IRB. All studies with a Management Plan include external members on the monitoring committees who are designated as the primary reviewer for the trial.

https://one.mskcc.org/sites/pub/Compliance/Policies/COMP-C001.pdf



APPENDIX: A. Protocol Review and Approval Flow Diagrams

B. Research Council Membership (Council A and B)

C. IRB/Privacy Board SOP List

D. DSM Committee Membership

E. DSMB Membership

F. OHRP Incident Report Form

G. Conflict of Interest Advisory Committee Membership



Appendix A: Protocol Review and Approval Flow Diagrams

MSK Investigator Initiated Trial (IIT) Committee Review Flow



External Protocol Committee Review Flow



Protocol Review Process forNCTN (Cooperative Group) Protocols

PI or designee obtains NCI CIRB approved protocol & consent

from CTSU

Institutional Review Board (IRB)MANDATORY

NCTN Sr. CRM submits local context documents to CIRB

for final approval

Committee on Radiation (COR) Review

IF APPLICABLE

Participating Department(s) (When Investigators are from other Departments)

Review based on Department guidelines

Department of Co-PI(s)

(When Co-PI is from another department)FULL PROTOCOL

REVIEW by Department

CommitteeMANDATORY

YES NO

Was the protocol and consent form approved by the NCI CIRB?

PI or designee obtains protocol & consent

from Network Group

Primary Departmental Review & Approval Process

(Service and/or DMT reviews at the discretion of the Primary Department)

FULL PROTOCOL REVIEW by Department Committee

MANDATORY

Primary Departmental Review & Approval Process

(Service and/or DMT reviews at the discretion of the Primary Department)

FULL PROTOCOL REVIEW by Department Committee

MANDATORY

MSK NCTN OfficeReview & Approval

MSK NCTN OfficeReview & Approval

Institutional Review Board (IRB)Research Authorization review only

MANDATORY

Participating Department

When study is multi-modality (i.e.

Chemotherapy and Radiation Therapy)

Department Committee Review

MANDATORY



Appendix B: Research Council Membership (Council A and B) Research Council A David H Ilson, MD, PhD, Co-Chair Department of Medicine, Gastrointestinal Oncology Service Valerie Rusch, MD, Co-Chair Department of Surgery, Thoracic Service Eric J Sherman, MD, Co-Chair Department of Medicine, Head and Neck Oncology Service Oguz Akin, MD Department of Radiology, Body Imaging Service Margaret Callahan, MD, PhD Department of Medicine, Melanoma and Immunotherapeutics Marinela Capanu, PhD Department of Epidemiology and Biostatistics, Biostatistics Service Daniel G Coit, MD Department of Surgery, Gastric & Mixed Tumor Service Anne Covey, MD Department of Radiology, Interventional Radiology Service Christopher Crane, MD Department of Radiation Oncology Sandra D’Angelo, MD Department of Medicine, Sarcoma Medical Oncology Service Gary Deng, MD Department of Medicine, Integrative Medicine Service Eli Louis Diamond, MD Department of Neurology Ira J Dunkel, MD Department of Pediatrics Ronald Ghossein, MD Department of Pathology, Surgical Pathology Service Alexia Iasonos, PhD Department of Epidemiology and Biostatistics, Biostatistics Service David P. Kelsen, MD Department of Medicine, Gastrointestinal Oncology Service Atif Khan, MD Department of Radiation Oncology Ola Landgren, MD, PhD Department of Medicine, Myeloma Service Robert Motzer, MD Department of Medicine, Genitourinary Oncology Service Garrett Nash, MD Department of Surgery, Colorectal Service Esperanza B Papadopoulos, MD Department of Medicine, Bone Marrow Transplant Service Raajit Rampal, MD, PhD Department of Medicine, Hematology Service Ann Rodavitch, MA Clinical Research Administration Jonathan E Rosenberg, MD Department of Medicine, Genitourinary Oncology Service Charles Michael Rudin, MD, PhD Department of Medicine. Thoracic Oncology Service Paul J Sabbatini, MD (Ex officio) Office of Physician-in-Chief Eytan Stein, MD Department of Medicine, Leukemia Service Tanya Trippett, MD Department of Pediatrics Robert Veselis, MD Department of Anesthesiology & Critical Care Medicine Hannah Wen, MD, PhD Department of Pathology, Surgical Pathology Service Roger S. Wilson, MD Department of Anesthesiology and Critical Care Medicine Anas Younes, MD Department of Medicine, Lymphoma Service Anthony Yu, MD Department of Medicine, Cardiology Service



Research Council B Kim Kramer, MD, Co-Chair Department of Pediatrics Christian Nelson, PhD, Co-Chair Department of Psychiatry and Behavioral Sciences, Psychiatry Dana Rathkopf, MD, Co-Chair Department of Medicine, Genitourinary Oncology Service Karen Autio, MD Department of Medicine, Genitourinary Oncology Service Margaret Barton-Burke, PhD, RN Department of Nursing Denise Correa, PhD Department of Neurology Aimee Crago, MD, PhD Department of Surgery, Gastric & Mixed Tumor Service Mark Dickson, MD Department of Medicine, Sarcoma Medical Oncology Service Pamela Drullinsky, MD Department of Medicine, Breast Medicine (Regional Networks) Lara Dunn, MD Department of Medicine, Head & Neck Oncology Service Elena Elkin, PhD Department of Epidemiology and Biostatistics Daphna Gelblum, MD Department of Radiation Oncology (Regional Networks) Jada Hamilton, MPH, PhD Department of Psychiatry & Behavioral Sciences, Behavioral Sciences Collette Houston Clinical Research Administration Geoffrey Ku, MD Department of Medicine, Gastrointestinal Oncology Service Mario Lacouture, MD Department of Medicine, Dermatology Service Michael LaQuaglia, MD Department of Surgery, Pediatric Surgical Service Peter Maslak, MD Department of Laboratory Medicine Sean McBride, MD Department of Radiation Oncology Shakeel Modak, MBBS, MD Department of Pediatrics Alison Moskowitz, MD Department of Medicine, Lymphoma Service Chaya Moskowitz, PhD Department of Epidemiology and Biostatistics, Biostatistics Service Sara Olson, PhD Department of Epidemiology and Biostatistics, Epidemiology Service Neeta Pandit-Taskar, MD Department of Radiology, Molecular Imaging & Therapy Service Sujata Patil, PhD Department of Epidemiology and Biostatistics, Biostatistics Service Michael A Postow, MD Department of Medicine, Melanoma & Immunotherapeutics Service Melissa Pulitzer, MD Department of Pathology James Root, PhD Department of Psychiatry & Behavioral Sciences, Psychiatry Service Paul J Sabbatini, MD (Ex officio) Office of Physician-in-Chief Talya Salz, PhD Department of Epidemiology & Biostatistics, Biostatistics Service Emily Tonorezos, MPH, MD Department of Medicine, General Internal Medicine Service Tiffany Traina, MD Department of Medicine, Breast Medicine Service Brian Untch, MD Department of Surgery, Head and Neck Service Herbert A. Vargas Alvarez, MD Department of Radiology



Appendix C: IRB/Privacy Board SOP List

IRB/PB SOPs

GENERAL ADMINISTRATION IRB/PB GA 101 Policies and Procedures Maintenance IRB/PB GA 102 Training and Education IRB/PB GA 103 Management of HRPP Office Staff IRB/PB GA 104 IRB Member and Consultant Conflict of Interest IRB/PB GA 105 IRB Signatory Authority IRB/PB GA 106 IRB of Record IRB/PB GA 107 Responsibilities of the IO

IRB/PB ORGANIZATION IRB/PB OP 201 Composition of IRB IRB/PB OP 202 Management of IRB IRB/PB OP 203 Duties of IRB Members IRB/PB OP 204 Undue Influence of IRB members and HRPP Office Staff

FUNCTION AND OPERATION IRB/PB FO 301 Authority and Purpose of the HRPP IRB/PB FO 302 Activities Requiring IRB Review IRB/PB FO 303 Research Exempt from IRB Review IRB/PB FO 304 Research Submission Requirements for Non-Exempt Research IRB/PB FO 305 IRB Meeting Administration IRB/PB FO 306 Administrative Review and Distribution of Materials IRB/PB FO 307 Documentation and Document Management IRB/PB FO 308 HIPAA and Research IRB/PB FO 309 Noncompliance in Human Research IRB/PB FO 310 Suspensions and Terminations of IRB Approval

REVIEW OF RESEARCH IRB/PB RR 401 Initial Review - Criteria for IRB Approval IRB/PB RR 402 Categories of Action IRB/PB RR 403 Reviews Utilizing the Expedited Procedure IRB/PB RR 404 Amendments to IRB Approved Research IRB/PB RR 405 Continuing Review - Criteria for Renewal IRB/PB RR 406 Advertisements and Recruitment Incentives IRB/PB RR 407 Deviations to IRB Approved Research and IRB SOPs IRB/PB RR 408 Reporting of Serious Adverse Events (ongoing continuing review) IRB/PB RR 409 Unanticipated Problems involving Risk to Participant or Others IRB/PB RR 410 Study Completion



REVIEWS REQUIRING SPECIAL CONSIDERATION IRB/PB SC 501 Vulnerable Populations IRB/PB SC 502 Gene Transfer Research IRB/PB SC 503 Genome-Wide Association Studies (GWAS) IRB/PB SC 504 Use of Germline DNA in MSK Sponsored Research IRB/PB SC 505 Genomic Advisory Panel Authority IRB/PB SC 506 Genomic Advisory Panel Administration IRB/PB SC 507 Genomic Advisory Panel - Member Composition IRB/PB SC 508 Genomic Advisory Panel - Member Duties IRB/PB SC 509 Emergency Use of a Test Article IRB/PB SC 510 Use of Investigational Drugs or Biologics in Human Research IRB/PB SC 511 Use of Investigational Devices in Human Research IRB/PB SC 512 Humanitarian Use Devices IRB/PB SC 513 Research Subject to DoD Regulations IRB/PB SC 514 Genomic Data Sharing (GDS)

IRB/PB COMMUNICATION IRB/PB CO 601 Communication with Investigative Staff IRB/PB CO 602 Communication with Other Entities

INFORMED CONSENT

IRB/PB IC 701 General Requirements for Informed Consent and HIPAA Research

Authorization IRB/PB IC 702 Waivers and Alterations of Informed Consent IRB/PB IC 703 Assent IRB/PB IC 704 Consenting Participants Who Do Not Read or Speak English IRB/PB IC 705 Consenting Professionals IRB/PB IC 706 Documentation of Informed Consent and Research Authorization

RESPONSIBILITIES OF INVESTIGATORS IRB/PB RI 801 Principal Investigators/Co-Principal Investigator Qualifications IRB/PB RI 802 Requirements for the Coordination of Multicenter Research Projects IRB/PB RI 803 Investigator Responsibilities

QUALITY ASSURANCE IRB/PB QA 901 QA/QC Program IRB/PB QA 902 Audits by Regulatory Agencies



Appendix D: DSM Committee Membership

Eileen O’Reilly, M.D. Chair, DSMC Attending Physician Department of Medicine, Gastrointestinal Oncology

Virginia Klimek, M.D. Associate Chair, DSMC

Associate Attending Physician Department of Medicine, Leukemia

Ronald Blum, M.D.* Professor of Medicine

Director, Cancer Centers and Programs Beth Israel Medical Center and St. Luke’s Roosevelt Hospital Jamie Chaft, M.D. Assistant Attending Physician Department of Medicine, Thoracic Guido Dalbagni, M.D. Attending Surgeon

Department of Surgery, Urology Nicola Fabbri, M.D. Attending Surgeon Department of Surgery, Orthopedic Josef Fox, M.D. Assistant Attending Radiologist Department of Radiology, Molecular Imaging & Therapy Igor Gavrilovic, M.D. Associate Attending Neurologist

Department of Neurology

Paul Hamlin, M.D. Associate Attending Physician Department of Medicine, Lymphoma Komal Jhaveri, M.D. Assistant Attending Physician Department of Medicine, Breast Mary Keohan, M.D. Associate Attending Physician Department of Medicine, Melanoma and Sarcoma

Meredith E. MacGregor, M.D. Instructor Department of Psychiatry & Behavioral Sciences, Psychiatry Vicky Makker, MD Assistant Attending Physician Department of Medicine, Gynecologic Medical Oncology



John Mulhall, MD Attending Surgeon Department of Surgery, Urology

Irina Ostrovnaya, Ph.D. Associate Attending Biostatistician Department of Epidemiology & Biostatistics

M. Lia Palomba, M.D. Associate Attending Physician Department of Medicine, Lymphoma

Genovefa Papanicolaou, M.D. Attending Physician Department of Medicine, Infectious Disease Miguel Perales, M.D. Associate Attending Physician

Department of Medicine, Bone Marrow Transplant Nitya Raj, M.D. Assistant Attending Physician Department of Medicine, Gastrointestinal Tanya Trippett, M.D. Associate Attending Pediatrician

Department of Pediatrics

Anna Varghese, M.D. Assistant Attending Physician Department of Medicine, Gastrointestinal Yoshiya Yamada, M.D. Attending Radiation Oncologist

Department of Radiation Oncology, Brachytherapy ∗ Consulting Member



Appendix E: DSMB Membership

Colin B. Begg, Ph.D. Attending Biostatistician Chair - DSMB Chair, Department of Epidemiology and Biostatistics

Memorial Sloan Kettering Cancer Center New York, NY

Eileen O’Reilly, M.D. Attending Physician

Gastrointestinal Oncology Service Department of Medicine

Memorial Sloan Kettering Cancer Center New York, NY Richard Gralla, M.D. Director of Oncology Research Jacobi Medical Center

Professor of Medicine Albert Einstein College of Medicine Bronx, NY David Harrington, Ph.D. Chair, Department of Biostatistical Science Dana-Farber Cancer Institute Boston, MA Franco Muggia, M.D. Professor of Oncology (Medicine)

NYU Cancer Institute New York University Medical Center New York, NY Suzanne Miller-Halegoua, Ph.D. Professor, Cancer Prevention and Control

Director, Psychosocial and Behavioral Medicine Program and Behavioral Research Core Facility

Fox Chase Cancer Center Philadelphia, PA



Appendix F: OHRP Incident Report Form



Appendix G: Conflict of Interest Advisory Committee Membership

Member Title Current Status

1 Peter Scardino, MD Attending Physician, Urology Service Chairman/Voting Member 2 Jose Baselga, M.D. Physician-in-Chief Voting Member 3 Deborah Berns, Esq SVP and Chief Risk Officer Voting Member

4 Ned Groves Senior Vice President and Chief Hospital Administrator Voting Member

5 Eric Cottington, PhD Senior Vice President, Research & Technology Management Voting Member

6 Cliff Hudis, MD Consultant, Breast Medicine Service Voting Member

7 Jason Lewis, PhD Chief, Radiochemistry and Imaging Service, Radiology and Director, Radiochemistry and Molecular Imaging Probe Core

Voting Member

8 Joan Massague, PhD Director, SKI Voting Member

9 Greg Raskin, M.D. Executive Director, Office of Technology Development Voting Member

10 Marilyn Resh, PhD SKI Member & Lab Head Voting Member

11 Greg Riely, MD Division Head Dept. of Medicine Voting Member

12 Vacant – Surgeon Department of Surgery Voting Member

Yashodhara Dash, PhD Senior Manager, Technology Management and Commercialization, OTD Non-Voting Member/Advisory

Carolyn Levine, Esq Deputy General Counsel and Corporate Secretary Non-Voting Member/Advisory

Mercedes Gorre Director, Office of the President Non-Voting Member/President Representative

Kristen Ahearn Associate General Counsel, Director, Compliance & Privacy Officer Non-Voting Member/Advisory

Malikah Fulton Institutional Compliance Manager, Conflict of Interest Non-Voting Member/Advisory

Marie Diaz Institutional Compliance Manager Non-Voting Member/Administrative

Documents

The MSK Policy document to ensure the highest quality ... · all of MSK’s facilities, increasing awareness and availability of trials to physicians and patients, enhancing our capacity